Method and apparatus for determining cardiac output

ABSTRACT

A method and apparatus for use in determining the cardiac output. The method include quantitatively measuring the patient&#39;s airflow, a first parameter indicative of the percent oxygen inhaled and exhaled by the patient, and a second parameter indicative of the patient&#39;s fractional arterial oxygen concentration. The method also includes inducing a change in the patient&#39;s arterial oxygen concentration while taking these measurements to monitor the effects of the change in the patient&#39;s arterial oxygen concentration. The cardiac output is determined from the data collected regarding the effects of the change in the patient&#39;s arterial oxygen concentration.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention pertains to a method and apparatus fordetermining the cardiac output of a patient, and, more particularly, toa method of determining cardiac output by analyzing the effect that aninduced change in the patient's arterial oxygen concentration has ontheir oxygen uptake and fractional arterial oxygen concentration, and toan apparatus for use in implementing such a method.

[0003] 2. Description of the Related Art

[0004] The are several generally accepted techniques for measuringcardiac output (CO), which is the total volumetric flow of blood throughthe heart, and, thus, through the body at any given time. Thesetechniques include: thermodilution, dye dilution, the direct Fickmethod, and partial CO₂ rebreathing. Thermodilution involves injectingcold saline directly into the right atrium of the heart and measuringthe temperature change downstream in the pulmonary artery using atemperature sensor placed in this artery. Cardiac output is determinedbased on this temperature change. Dye dilution is similar tothermodiluation except that a dye, rather than cold saline, is injectedinto the art. The amount of dye collected downstream is measured todetermine the patient's cardiac output.

[0005] According to the direct Fick method, either the content of oxygen(O₂) or the content of carbon dioxide (CO₂) in both the arterial bloodand mixed venous blood are measured. The Fick equation, written foroxygen, is: CO=O₂ uptake/(the content of O₂ in arterial blood−thecontent of O₂ in mixed venous blood). The Fick equation, written forcarbon dioxide, is: CO=CO₂ excreted/(the content of CO₂ in mixed venousblood−the content of CO₂ in arterial blood). As noted above, the directFick method requires obtaining a mixed venous blood sample, which isonly available in the pulmonary artery. See FIG. 1.

[0006] It can thus be appreciated that thermodilution, dye dilution, andthe direct Fick method for determining cardiac output all requireinsertion of a catheter into the patient at, near, or through the heart.More specifically, in implementing these cardiac output measurements, acatheter is usually floated through the chambers of the heart in orderto insert the saline or dye or to obtain the necessary blood sample atthe correct location. For this reason, either of the above cardiacoutput measurement techniques is very invasive. Indeed, it is known thatan arrhythmia may result from the placement of the catheter in orthrough the heart. Therefore, these cardiac output measurementtechniques are typically only performed in the most critical ofsituations, where the need to know the patient's cardiac outputoutweighs the risk to the patient in taking this measurement.

[0007] The partial CO₂ rebreathing technique for measuring cardiacoutput, on the other hand, is a noninvasive approach believed to havebeen developed by Novametrix Medical Systems, Inc. of Wallingford, Conn.(Novametrix). This method is implemented using a device referred to as aNICO™ sensor, which is distributed by Novametrix. The NICO sensormeasures the flow of gas to and from the patient and the CO₂ content inthe patient's exhaled gas.

[0008] The partial CO₂ rebreathing cardiac output measurement techniqueis based on the CO₂ Fick equation in conjunction with what is calledpartial CO₂ rebreathing. According to this partial CO₂ rebreathingtechnique, cardiac output is measured by comparing the patient's CO₂excretion to the arterial CO₂ content during normal breathing and duringrebreathing, in which the patient rebreathes expired gases for a periodof time. Cardiac output is determined as: CO=the change in CO₂excretion/the change in the arterial CO₂ content.

[0009] Arterial CO₂ is typically determined from a sample of arterialblood. However, in order to eliminate the need for a blood sample tomeasure the arterial CO₂ content, the partial CO₂ rebreathing techniquesubstitutes end tidal CO₂ (ETCO₂) for the required arterial CO₂measurement. Therefore, the cardiac output equation becomes: CO=thechange in CO₂ excretion/the change in the ETCO₂.

[0010] This partial CO₂ rebreathing technique, however, has severaldisadvantages. Namely, the patient is preferably intubated or breathingthrough a trachea tube when taking the flow and CO₂ measurements tocapture the total volume of CO₂. In addition, the patient must beheavily sedated or unconscious so that he or she is not breathingspontaneously. If the patient is breathing spontaneously, the increasedCO₂ level in the blood during the rebreathing phase would automaticallytrigger the patient's respiratory system to speed up or deepen thebreaths to remove the excess CO₂. It is well known that for mostpatient's the level of CO₂, not the level of O₂, is the mechanism fortriggering ventilation. Such rapid or deep breathing prevents anaccurate determination of cardiac output under this technique. It shouldalso be noted that the use of end tidal CO₂, as opposed the arterial CO₂content, may introduce errors in determining cardiac output, because theare situations where the end tidal CO₂ may not correlate with thearterial CO₂ content. The partial CO₂ rebreathing cardiac outputmeasurement technique is also disadvantageous because it does notadequately account for shunt blood flow, which is blood that is notoxygenated during the respiratory cycle. This flow cannot be directlymeasured, but must be estimated when using this conventional cardiacoutput measurement technique.

SUMMARY OF THE INVENTION

[0011] Accordingly, it is an object of the present invention to providea method of measuring cardiac output that overcomes the shortcomings ofconventional cardiac output measurement techniques. This object isachieved according to one embodiment of the present invention byproviding a cardiac output measurement method that includesquantitatively measuring a patient's airflow, a first parameterindicative of a percent oxygen inhaled and exhaled by the patient, and asecond parameter indicative of the patient's fractional arterial oxygenconcentration. The present method also includes inducing a change in thepatient's arterial oxygen concentration and repeating these measurementsto monitor the effects resulting from inducing the change in thepatient's arterial oxygen concentration. The patient's cardiac output isdetermined based on the data collected.

[0012] It is yet another object of the present invention to provide anapparatus for non-invasively determining the cardiac output of apatient, including a spontaneously breathing patient, that does notsuffer from the disadvantages associated with conventional cardiacmeasurement systems. This object is achieved by providing an apparatusthat includes a patient flow measuring system capable of quantitativelymeasuring a patient's airflow, i.e., the flow of gas to and from apatient, an oxygen analyzing system adapted to measure a first parameterindicative of a percent oxygen inhaled and exhaled by such a patient,and means for measuring a second parameter indicative of the patient'sfractional arterial oxygen concentration, such as a pulse oximeter. Aprocessor determines the cardiac output based on the measured patientairflow, the first parameter, and the second parameter. In addition, anoutput device outputs the result indicative of the patient's cardiacoutput.

[0013] These and other objects, features and characteristics of thepresent invention, as well as the methods of operation and functions ofthe related elements of structure and the combination of parts andeconomies of manufacture, will become more apparent upon considerationof the following description and the appended claims with reference tothe accompanying drawings, all of which form a part of thisspecification, wherein like reference numerals designate correspondingparts in the various figures. It is to be expressly understood, however,that the drawings are for the purpose of illustration and descriptiononly and are not intended as a definition of the limits of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014]FIG. 1 is a schematic diagram of mammalian cardiopulmonary system;

[0015]FIG. 2 is an oxygen-hemoglobin dissociation curve for a human;

[0016]FIG. 3 is a graph illustrating the change in oxygen uptake thattakes place during an induced change in arterial oxygen concentrationaccording to the cardiac output measurement method of the presentinvention;

[0017]FIG. 4 is a graph illustrating the change in arterial oxygensaturation resulting from the induced change in arterial oxygenconcentration;

[0018]FIGS. 5 and 6 are graphs illustrating the change in oxygen uptakeand arterial oxygen concentration, respectively, resulting from theinduced change in arterial oxygen concentration including the potentialeffects of recirculation;

[0019]FIGS. 7 and 8 are graphs illustrating the change in oxygen uptakeand arterial oxygen concentration, respectively, resulting from theinduced change in arterial oxygen concentration illustrating analternative embodiment for determining cardiac output based on thesechanges;

[0020]FIGS. 9 and 10 are graphs illustrating the change in oxygen uptakeand arterial oxygen concentration, respectively, resulting from theinduced change in arterial oxygen concentration illustrating yet anotheralternative embodiment for determining cardiac output based on thesechanges;

[0021]FIG. 11 is a schematic diagram of a device for implementing thecardiac output measurement method of the present invention; and

[0022]FIG. 12 is a schematic diagram of the device of FIG. 11 shown inuse on a patient.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS OF THEINVENTION

[0023]FIG. 1 schematically illustrates a patient's cardiopulmonarysystem, which is useful in understanding the cardiac output measurementsystem of the present invention. The cardiac output measurementtechnique of the present invention measures the output, i.e., rate offlow of blood, from the left side of the heart. As described in detailbelow, the cardiac output measurement method of the present inventionuses the transfer of oxygen from the lungs to the arteries in order todetermine cardiac output.

[0024] The presently preferred method of determining the cardiac outputincludes the following steps, each of which is discussed in detailbelow:

[0025] (1) quantitatively measuring (a) the patient's airflow, (b) aparameter indicative of the percent oxygen inhaled and exhaled by thepatient, and (c) a parameter indicative of the patient's fractionalarterial oxygen concentration (XaO₂);

[0026] (2) inducing a change in the patient's arterial oxygenconcentration while taking measurements (a)-(c) set forth in step (1) tomonitor the effects of the change in the patient's arterial oxygenconcentration; and

[0027] (3) from the data collected regarding the effect of the change inthe patient's arterial oxygen concentration, determining the patient'scardiac output.

[0028] According to the present invention, the patient's cardiac output(CO) is determined based on the change in oxygen uptake versus thechange in fractional arterial oxygen concentration resulting from theinduced change in the arterial oxygen concentration. Stated another way:$\begin{matrix}{{CO} = {\frac{{change}\quad {in}\quad {the}\quad {oxygen}\quad {uptake}}{{change}\quad {in}\quad {the}{\quad \quad}{arterial}\quad {oxygen}\quad {concentration}}.}} & (1)\end{matrix}$

[0029] It is important to note that the patient's arterial oxygenconcentration, not their carbon dioxide concentration, is what is beingmanipulated in order to induce a change in the patient's oxygen uptakeand fractional arterial oxygen concentration. As a result, this methodcan be performed on a spontaneously breathing patient, as well as apatient who is not spontaneously breathing. Unlike changing thepatient's CO₂ concentration, changing the patient's arterial O₂concentration will not cause the patient to automatically attempt toalter their breathing pattern to move the O₂ concentration back tonormal. Because this cardiac output measurement technique involvesinducing a change in the patient's arterial oxygen concentration, it isreferred to as an oxygen concentration modification cardiac outputmeasurement method.

[0030] In one embodiment of the present invention, which is described indetail below, the patient's fractional arterial oxygen concentration ismeasured non-invasively using a conventional pulse oximeter. Thus,unlike conventional cardiac output measurement methods, the oxygenconcentration modification cardiac output measurement method of thepresent invention can be performed non-invasively on a spontaneouslybreathing patient.

[0031] I. Measuring Airflow, Percent O₂ Inhaled/Exhaled, and theFractional Arterial Oxygen Concentration

[0032] According to the present invention, the patient's quantitativeairflow and a parameter indicative of the percent oxygen inhaled andexhaled by the patient are measured to determine the patient's oxygenuptake. Oxygen uptake is the amount of oxygen absorbed into the blood inthe lungs. It is typically expressed in liters as VO₂ or in liters perminute (lpm) as {dot over (V)}O₂. Thus, equation (1) can be rewritten asfollows: $\begin{matrix}{{{{CO}({liters})} = \frac{\Delta \quad {VO}_{2}}{\Delta \quad {XaO}_{2}}},{{or}\quad {as}}} & (2) \\{{{CO}({lpm})} = {\frac{\Delta \quad \overset{.}{V}\quad O_{2}}{\Delta \quad {XaO}_{2}}.}} & (3)\end{matrix}$

[0033] Oxygen uptake, which is measured during a breathing cycle, isdetermined by measuring the volumetric airflow Q_(patient) to and fromthe patient, the %O₂ inhaled, and the %O₂ exhaled during that breathingcycle. Volumetric airflow is measured using a flow meter, such as aconventional pneumotach, that is capable of quantitatively measuring theflow of gas to and from the patient's airway. U.S. Pat. No. 6,017,315 toStarr et al., the contents of which are incorporated herein byreference, describes a suitable flow meter that quantitatively measuresthe flow of gas to and from a patient.

[0034] The %O₂ inhaled and %O₂ exhaled is measured using a conventionaloxygen analyzer. An example of a combination flow sensing element and O₂concentration analyzer window suitable for use in the present inventionis taught in provisional U.S. patent application No. 60/170,918, thecontents of which are incorporated herein by reference. Morespecifically, the present invention contemplates determining the %O₂inhaled by measuring the patient's fraction of inspired oxygen (FIO₂) asa parameter indicative of the percent oxygen inhaled and exhaled, andmultiplying this FIO₂ by 100, i.e., %O₂ inhaled=FIO₂ (inhaled) * 100. Asimilar process is used to determine %O₂ exhaled.

[0035] Oxygen uptake, V0₂, for one breath, is determined as follows:$\begin{matrix}{{{{VO}_{2}{inhaled}} = {\int_{t_{1}}^{t_{2}}{\left( {Q_{patient}\left\lbrack {\% {O_{2}/100}} \right\rbrack} \right)\quad {t}}}},} & (4) \\{{{{VO}_{2}{exhaled}} = {\int_{t_{2}}^{t_{3}}{\left( {Q_{patient}\left\lbrack {\% {O_{2}/100}} \right\rbrack} \right)\quad {t}}}},{and}} & (5)\end{matrix}$

 VO₂ =VO₂inhaled−VO₂exhaled,  (6)

[0036] where t₁ is the start of inhalation, t₂ is the end of inhalationor start of exhalation, and t₃ is the end of exhalation. Oxygen uptakein liters per minute is then determined as:

VO₂ =VO₂*f_(breath),  (7)

[0037] were f_(breath) is the frequency of breaths, i.e., breaths perminute.

[0038] There are a variety of parameters indicative of fractionalarterial oxygen concentration, XaO₂, of a patient that can be measuredand used in the cardiac output determination method. One embodiment ofthe present invention contemplates measuring at least one the followingblood gas constituents, SaO₂, PaO₂, and CaO₂ as the parameter indicativeof the patient's fractional arterial oxygen concentration XaO₂. Theseparameters are measured from an arterial blood sample or using acontinuously indwelling catheter. It is preferable for one or more ofthese constituents to be measured continuously, for example, using anindwelling catheter so that the effects of the induced change inarterial oxygen concentration on the oxygen uptake and fractionalarterial oxygen concentration can be monitored on a substantiallycontinuous basis. This is especially important because of the relativelyshort duration of the effects of the induced change in arterial oxygenconcentration resulting from the oxygen concentration modification step.

[0039] The present invention also contemplates measuring the pulseoximetry oxygen saturation level (SpO₂) of the patient as the parameterindicative of the fractional arterial oxygen concentration XaO₂. Thismeasurement is advantageous in that the SPO² can be measurednon-invasively using a conventional pulse oximeter. It can also be takenon a generally continuous basis to closely monitor the effects of theinduced oxygen concentration modification on the patient's actualfractional arterial oxygen concentration.

[0040] Although the SpO2 level can be taken from almost any location onthe patient, such as the finger or ear, in a preferred embodiment, theSpO2 is measured across the nasal septum. This location is especiallydesirable because it represents a relatively direct flow from thecarotid artery, as shown in FIG. 1.

[0041] Depending on which parameter, SpO2, SaO₂, PaO₂, or CaO₂,indicative of fractional arterial oxygen concentration XaO₂ is measured,a conversion may be required in order to arrive at the patient's actualfractional arterial oxygen concentration XaO₂. The only parameterindicative of fractional arterial oxygen concentration XaO₂ that doesnot have to be converted in order to arrive at the patient's fractionalarterial oxygen concentration XaO₂ is the arterial oxygen contentmeasurement CaO₂, because CaO₂ is a direct measurement of the fractionalarterial oxygen concentration. Thus, CaO₂=XaO₂, and no conversion isnecessary.

[0042] Oxygen saturation, SaO₂, on the other hand, is not a directmeasurement of the fractional arterial oxygen concentration XaO₂. IfSaO₂ is the measured parameter, a conversion is needed, so that themeasured SaO₂ can be used as the fractional arterial oxygenconcentration XaO₂. For a normal adult, there is a linear relationbetween SaO₂ and CaO₂ and, hence, between SaO₂ and XaO₂. Morespecifically, the following relationship is known:

[0043] Vol % O₂=(Hb concentration)(O₂ saturation (SaO₂) )(O₂ carryingcapacity of Hb), (8) where, for a normal adult, the O₂ carrying capacityof hemoglobin (Hb) is approximately 1.34 mlO₂/gmHb, and the Hbconcentration is approximately 15 gmHb/100 mlblood. Thus, for a normaladult: $\begin{matrix}{{XaO}_{2} = {\frac{{Vol}\% O_{2}}{100} = {\frac{15\quad {gmHb}}{100\quad {mlbood}}*\frac{{SaO}_{2}}{100}*{\frac{1.34\quad {mlO}_{2}}{gmHB}.}}}} & (9)\end{matrix}$

[0044] Equation (9) can be simplified as:

XaO₂ =SaO₂ *k,  (10)

[0045] where, for a normal adult: $\begin{matrix}{k = {\frac{(15)(1.34)}{(100)(100)}.}} & (11)\end{matrix}$

[0046] Of course, the values for Hb concentration (15 gmHb) and O₂carrying capacity of Hb (1.34 mlO₂) can differ depending on theindividual. Therefore, if the Hb concentration and O₂ carrying capacityof Hb for an individual are known, a more exact relationship (k value)between SaO₂ and XaO₂ can be determined. The present inventioncontemplates that the values for Hb concentration and/or O₂ carryingcapacity of Hb can be directly input by the user, automatically inputfrom measurements taken by a co-oximeter or other equivalent device viaa communication link with such a device, manually or automaticallyselected from a range of values based on information about the patient,or a default value can be used.

[0047] There is also a known relationship, albeit nonlinear, betweenPaO₂ and SaO₂. This nonlinear relationship is graphically depicted inFIG. 2, which is referred to as an oxygen-hemoglobin dissociation curve10. If PaO₂ is the measured parameter, it must first be converted to anSaO₂ using the dissociation curve, which can be accomplished using anyconventional technique. Thereafter, the conversion factor k for SaO₂must be used to arrive at the patient's fractional arterial oxygenconcentration XaO₂ as discussed above.

[0048] A patient's SaO₂, PaO₂, or CaO₂ can only be measured by samplingthe patient's arterial blood or using a continuously indwellingcatheter, either of which is a relatively invasive procedure. SpO₂, onthe other hand, which is an estimation of SaO2, is measurednon-invasively. Therefore, measuring the patient's SpO2 has theadvantage of being fast, easy, and non-invasive. If SpO₂ is taken as themeasured parameter, it is considered an approximation of SaO₂, i.e.,SpO2 SaO₂. Thus, the conversion factor k is applied to the measured SpO2to arrive at the patient's fractional arterial oxygen concentrationXaO₂, i.e., XaO₂=SpO_(2 *) k.

[0049] II. Inducing a Change in Arterial Oxygen Concentration

[0050] The present technique for determining a patient's cardiac outputinvolves inducing a change the patient's arterial oxygen concentration.This can be done in a variety of ways, several of which are discussedbelow, so long as there is a measurable difference between the patient'sbaseline arterial oxygen concentration and the patient's arterial oxygenconcentration following the induced change therein. Because the goal ofthis process is to force a change in the patient's arterial oxygenconcentration, this step in the cardiac output measurement process ofthe present invention is referred to herein as the “oxygen concentrationmodification step.”

[0051] It should be noted that the arterial oxygen concentration caneither be increased or decreased depending on the condition of thepatient. For example, a generally healthy patient has an oxygensaturation level of approximately 98%. As a result, there is very littleroom to improve oxygenation, e.g., up to 99%. Therefore, the presentinvention contemplates reducing the patient's oxygen saturation as onetechnique for inducing a change in the patient's arterial oxygenconcentration, especially in those patients with a relatively highbaseline SaO₂.

[0052] Reducing the patient's oxygen saturation can be accomplished byreducing the fraction of inspired oxygen (FIO₂) in the patient's inhaledgas. This can be accomplished, for example, by increasing theconcentration of other inhaled gas constituents, such as nitrogen, whichas the effect of lowering the patient's arterial oxygen saturation. Inone embodiment of the present invention, the patient breathes nitrogenfor one or more breaths, thereby reducing their arterial oxygenconcentration. This technique is particularly suited for patients with arelatively high baseline oxygen concentration.

[0053] As noted above, changing the patient's arterial oxygenconcentration can also be accomplished by increasing the fraction ofinspired oxygen in the inhaled gas. This can be accomplished, forexample, by adding supplemental oxygen to the patient's inhaled gas,and, therefore, is particularly suited for patients with a relativelylow baseline oxygen concentration.

[0054] The present invention also contemplates changing the patient'sarterial oxygen concentration by having the patient rebreathe expiredgas. However, because this will raise the patient's CO₂ level, thistechnique is best used on non-spontaneously breathing patients, whereincreased levels of CO₂ will not cause unusual breathing patterns. For anon-spontaneously breathing patient, the present invention alsocontemplates changing the arterial oxygen concentration by momentarilypausing the ventilator used to provide the patient's breathing.

[0055] Rebreathing expired gas can be used to change the patient'sarterial oxygen concentration in a spontaneously breathing patient ifsteps are taken to minimize the increase in the patient's CO₂ level. Forexample, the carbon dioxide CO₂ is preferably is removed from therebreathed gas so that the patient does not dramatically alter theirbreathing pattern due to rebreathing of exhaled carbon dioxide.

[0056] An exemplary embodiment of the present invention contemplatesusing a conventional CO₂ “scrubbing” technique for removing the CO₂ fromthe gas rebreathed by the patient. This is accomplished, for example, byplacing a CO₂ scrubber in the rebreathing circuit or by passing thepatient's exhaled gas through a CO₂ scrubber before it is returned tothe patient. In either case, the rebreathed gas will have a lower oxygenconcentration, thereby accomplishing the goal of changing the patient'sarterial oxygen concentration without having the patient breathing CO₂,which will likely trigger a relatively rapid increase in the patient'sbreath rate.

[0057] Ill. Determining Cardiac Output

[0058] The present invention contemplates several techniques forcalculating cardiac output based on the changes in oxygen uptake and thechange in fractional arterial oxygen concentration resulting from theinduced change in arterial oxygen concentration. Each of thesetechniques is discussed in turn below.

[0059] A. Technique 1 —Calculating Cardiac Output Based on the AreaUnder the Curves

[0060] It is well known that the rate of flow (Q) of a fluid, which istypically expressed in liters per minute (lpm), is defined as:$\begin{matrix}{{Q = \frac{V}{t}},} & (12)\end{matrix}$

[0061] where V is volume and t is time. For a given period of time,t_(a) to t_(b), the rate of flow of fluid during that period isdetermined as follows: $\begin{matrix}{Q = \frac{V}{t_{b} - t_{a}}} & (13)\end{matrix}$

[0062] The following relationships are also known: $\begin{matrix}{{{XaO}_{2} = \frac{{VO}_{2}}{V}},{or}} & (14)\end{matrix}$

$\begin{matrix}{V = {\frac{{VO}_{2}}{{XaO}_{2}}.}} & (15)\end{matrix}$

[0063] Substituting equation (14) into equation (13) yields:$\begin{matrix}{Q = {\frac{{VO}_{2}}{{XaO}_{2}*\left( {t_{b} - t_{a}} \right)}.}} & (16)\end{matrix}$

[0064] Equation (16), however, cannot be used to determine a patient'scardiac output because it does not take into consideration the fact thatin the pulmonary system, the venus blood contains a predetermined levelof oxygen before it is oxygenated in the lungs. In addition, thisequation does not take into consideration blood that is shunted acrossthe lungs and does not get oxygenated during a breathing cycle.

[0065] The present invention takes these items into consideration andaccounts for their effect by, in essence, determining the baselineoxygen concentration and oxygen uptake for the patient, then executingthe oxygen concentration modification step, in which the patient'sfractional arterial oxygen concentration is changed from the baselinevalue. The present invention determines cardiac output by monitoring thearterial oxygen concentration and oxygen uptake during this oxygenconcentration modification step and by comparing the changes in thearterial oxygen concentration and oxygen uptake to the baseline levels.

[0066]FIG. 3 is a graph that illustrates the change in a patient'soxygen uptake, VO₂, that takes place during the oxygen concentrationmodification step, in which a change in the arterial oxygenconcentration, XaO₂, is induced using any of the above-describedtechniques. More specifically, FIG. 3 illustrates the change in oxygenuptake that takes place by having the patient take one breath, i.e.,from time t₁ to t₃, that is relatively devoid of oxygen. It should benoted that the change in oxygen uptake is illustrated in a step fashionbecause oxygen uptake is measured and calculated on a breath-by-breathbasis. As shown in FIG. 3, it takes several breaths for the patient'soxygen uptake to stabilize back to its baseline level. Area A in FIG. 3represents the change in the oxygen uptake ΔVO₂ of the patient thatoccurs as a result of oxygen concentration modification step.

[0067]FIG. 4 illustrates the change in arterial oxygen saturation SaO₂resulting from the induced change in arterial oxygen concentration,which, in this embodiment, involves having the patient take one breaththat is devoid of oxygen. Area B in FIG. 4 represents the change inarterial oxygen concentration ΔXaO₂ that occurs as a result of oxygenconcentration modification step. These changes are measured and used tocalculate cardiac output as follows: $\begin{matrix}{{Q = \frac{\Delta \quad {VO}_{2}}{\Delta \quad {XaO}_{2}*\left( {t_{b} - t_{a}} \right)}},} & (17)\end{matrix}$

[0068] where:

ΔVO₂ =VO_(2baseline)−VO_(2after oxygen concentration modification)  (18)

ΔXaO₂ =XaO_(2baseline)−XaO_(2after oxygen concentration modification)  (19)

[0069] It can be appreciated from FIGS. 3 and 4 that although thepatient takes only one breath that is devoid of oxygen, the patient'soxygen uptake will shift from its baseline level for several breathsi.e., from time t_(a) to time t_(b). Therefore, the present inventioncontemplates summing the oxygen uptake that occurs for each breath overthe entire time, t_(a) tot_(b), that the oxygen uptake is shifted frombaseline, which, in effect, amounts to determining the area A under thecurve, which is why this technique is referred to in the section headingas “Calculating Cardiac Output Based on the Area Under the Curves.”

[0070] The patient's arterial oxygen concentration will also shift fromits baseline level for a period of time t_(c) to t_(d). Therefore, thepresent invention contemplates finding the average arterial oxygenconcentration resulting from the oxygen concentration modification step.It should be noted that the change in arterial oxygen concentration doesnot coincide with the start of the oxygen concentration modificationstep, i.e., t_(c) ≠ t_(a), because it takes some time for the change ininspired oxygen level to affect the patient's arterial oxygenconcentration. Thus, equation (19) for the present invention isrewritten as: $\begin{matrix}{Q = {\frac{\sum{\Delta \quad {VO}_{2}}}{\Delta \quad \overset{\_}{X}\quad {aO}_{2}*\left( {t_{b} - t_{a}} \right)}.}} & (20)\end{matrix}$

[0071] Equation (20) can be written in greater detail as:$\begin{matrix}{{Q = \frac{\sum\left( {{VO}_{2\quad {baseline}} - {VO}_{2\quad {after}\quad {oxygen}\quad {concentration}\quad {modification}}} \right)_{t_{b} - t_{a}}}{\int_{t_{c}}^{t_{d}}{\left\lbrack \frac{\begin{matrix}{{{Sp}O}_{2\quad {baseline}} -} \\{{Sp}O}_{2\quad {after}\quad {oxygen}\quad {concentration}\quad {modification}}\end{matrix}}{\left( {t_{d} - t_{c}} \right)}\quad \right\rbrack {t}*\left( {t_{b} - t_{a}} \right)}}},{{where}:}} & (21) \\{{VO}_{2} = {{\int_{t_{1}}^{t_{2}}{\left( {Q_{patient}\left\lbrack {\% {O_{2}/100}} \right\rbrack} \right)\quad {t}}} - {\int_{t_{2}}^{t_{3}}\left( {{Q_{patient}\left\lbrack {\% {O_{2}/100}} \right\rbrack}\quad {{t}.}} \right.}}} & (22)\end{matrix}$

[0072] FIGS. 5 and 6 are similar to FIGS. 3 and 4, respectively, exceptthat FIGS. 5 and 6 take into consideration a scenario in which thepatient's blood begins to recirculate at time x during the oxygenconcentration modification step. It can be appreciated from FIG. 5, thatthe patient's oxygen uptake may increase above baseline and theneventually return to its baseline level at time tbl. It this situation,the only area of interest is the area under the baseline, i.e., area Al.That is, the effects of recirculatation, and, hence, area A₂ should beignored in solving equation (21). For this reason, the present inventioncontemplates extrapolating to determine the baseline crossing point,which corresponds to point t_(b) in equation (21). Thus, the change inoxygen uptake resulting from the oxygen concentration modification step,in this situation, will take into consideration the sum of areas A₁ andA₂ for purpose of solving equation (21), ignoring area A₃ above thebaseline.

[0073]FIG. 6 illustrates that a second drop in the patient's arterialoxygen saturation will occur at time x due to the recirculation of therelatively oxygen poor blood. If this second drop, which is representedby area B₂, is minimal, it can be ignored for purposes of determiningthe time period t_(c) to t_(d). Thus, the time period t_(c) to t_(d2)associated with areas B₁ and B₂ are used to solve equation (21).

[0074] However, if this second drop is not minimal, the time periodt_(c) to t_(d1) associated with area B₁ alone is used for solvingequation (21). The location of time t_(d1) is determined using anyconventional extrapolation technique. Of course, the present inventioncontemplates using suitable programming or other means for deciding whenthe effect of recirculation, and, hence the size of area B₂ is above thepredetermined minimal threshold and must be accounted for in solvingequation (21).

[0075] B. Technique 2—Calculating Cardiac Output Based on the Slopes ofthe Curves

[0076]FIGS. 7 and 8, like FIGS. 3 and 4, illustrate the changes in thepatient's oxygen uptake and arterial oxygen saturation, respectively,resulting from the oxygen concentration modification step. From FIG. 7,it can be appreciated that the change in oxygen uptake that takes placeduring the first breath of the oxygen concentration modification stepcan be defined in terms of its slope as: $\begin{matrix}{{{\Delta \quad {VO}_{2}} = {\frac{\Delta \quad y}{\Delta \quad x} = {\frac{y_{2} - y_{1}}{x_{2} - x_{1}} = \frac{{{VO}_{2}\left( t_{3} \right)} - {{VO}_{2}\left( t_{1} \right)}}{t_{3} - t_{1}}}}},} & (23)\end{matrix}$

[0077] recall from above that t₁ corresponds to the start of inspirationand that t₃ corresponds to the end of expiration, and where VO₂(t₁) andVO₂(t₃) are the oxygen uptakes at times t₁ and t₃, respectively. It canbe further appreciated that equation (23) defines the slope of dashedline C in FIG. 7.

[0078] From FIG. 8, it can be appreciated that that the change infractional arterial oxygen concentration that takes place during thesame time period t₃−t₁ can also be defined in terms of its slope as:$\begin{matrix}{{{\Delta \quad \left( {{Xa}O} \right)_{2}} = \frac{{{XaO}_{2}\left( t_{5} \right)} - {{XaO}_{2}\left( t_{4} \right)}}{t_{5} - t_{4}}},} & (24)\end{matrix}$

[0079] where, t₅−t₄=t₃'t₁, and where XaO₂(t₅) and XaO₂(t₄) are thearterial oxygen concentration at times t₅ and t₄, respectively. It canbe further appreciated that equation (24) defines the slope of dashedline D in FIG. 8. Therefore, this cardiac output determination techniqueis referred to in the immediately preceding section heading as the“Slopes of the Curve” technique. From equation (15) it is known that:$\begin{matrix}{{\Delta \quad V} = {\frac{{\Delta VO}_{2}}{{\Delta XaO}_{2}}.}} & (25)\end{matrix}$

[0080] Substituting equations (23) and (24) in to equation (25) yields:$\begin{matrix}{{\Delta \quad V} = {{\left\lbrack \frac{{{VO}_{2}\left( t_{3} \right)} - {{VO}_{2}\left( t_{1} \right)}}{t_{3} - t_{1}} \right\rbrack \left\lbrack \frac{t_{5} - t_{4}}{{{XaO}_{2}\left( t_{5} \right)} - {{XaO}_{2}\left( t_{4} \right)}} \right\rbrack}.}} & (26)\end{matrix}$

[0081] From equations (13) and (26), the patient's cardiac output Q inliters per minute is defined as: $\begin{matrix}{Q = {\frac{\Delta \quad V}{t_{3} - t_{1}} = {{\left\lbrack \frac{{{VO}_{2}\left( t_{3} \right)} - {{VO}_{2}\left( t_{1} \right)}}{\left( {t_{3} - t_{1}} \right)^{2}} \right\rbrack \left\lbrack \frac{t_{5} - t_{4}}{{{XaO}_{2}\left( t_{5} \right)} - {{XaO}_{2}\left( t_{4} \right)}} \right\rbrack}.}}} & (27)\end{matrix}$

[0082] It can be appreciated that determining cardiac output based onthe slopes of lines C and D is advantageous in that the effects ofrecirculation, if any, do not influence the determination of cardiacoutput.

[0083] C. Technique 3—Calculating Cardiac Output Based on the Magnitudeof the Curves

[0084] Yet another technique for determining cardiac output involvescomparing the magnitude of the change in oxygen uptake with themagnitude of the change in arterial oxygen concentration resulting fromthe oxygen concentration modification step. FIGS. 9 and 10 illustratethe changes in the patient's oxygen uptake and arterial oxygensaturation, respectively, resulting from the oxygen concentrationmodification step. From FIG. 9, it can be appreciated that there is arelatively large initial drop in oxygen uptake at the start of theoxygen concentration modification step, i.e., from time t₁ to t₃. Themagnitude of this drop can be determined from the output of the flowsensor and the oxygen analyzer using any conventional technique. FromFIG. 10, it can be appreciated that there is corresponding drop inarterial oxygen saturation. Although, as noted above, this drop inarterial oxygen concentration is delayed in time from the initial dropin oxygen uptake. This drop begins at time t_(c) and reaches a maximumdifference from the initial baseline level at time t_(m). The value ofthe fractional arterial oxygen concentration at t_(m), XaO₂(t_(m)), canbe determined using any conventional technique.

[0085] As a side note, it is worth remembering that the oxygenconcentration modification step also contemplates increasing thepatient's arterial oxygen in some situations. In which case, the changein oxygen uptake will be in the positive direction, opposite that shownin FIGS. 3, 5, 7, and 9. Similarly, the change in the fractionalarterial oxygen concentration will also be in the positive direction,opposite that shown in FIGS. 4, 6, 8, and 10. The techniques fordetermining cardiac output discussed herein are equally applicable wherethe oxygen concentration modification step in performed by increasingthe patient's arterial oxygen.

[0086] Referring again to FIGS. 9 and 10, one embodiment of the presentinvention contemplates comparing the magnitude of the change in oxygenuptake from time t₁ to t₃ with the magnitude of the change in arterialoxygen concentration from time t_(c) to t_(m), so that the patient'scardiac output is defined as: $\begin{matrix}{{CO} = {\frac{\frac{\Delta \quad {{VO}_{2}\left( {{Magnitude}\quad t_{1}\quad {to}\quad t_{3}} \right.}}{t_{3} - t_{1}}}{{XaO}_{2}\left( {{Magnitude}\quad t_{c}\quad {to}\quad t_{m}} \right)} = {\frac{\Delta \quad \overset{.}{V}\quad {O_{2}\left( {{Magnitide}\quad t_{1}\quad {to}\quad t_{3}} \right)}}{\Delta \quad {{XaO}_{2}\left( {{Magnitide}\quad t_{c}\quad {to}\quad t_{m}} \right)}}.}}} & (28)\end{matrix}$

[0087] It can be appreciated that equation (28) represents a directcalculation for cardiac output because the units represented by thenumerator are, for example, liters/second or liters/minute, and thedenominator is unitless.

[0088] Another embodiment of the present invention contemplatesdetermining cardiac output based on the time period t_(c) to t_(e),where t_(c) to t_(c)=t₁ to t₃, so that $\begin{matrix}{{CO} = {\frac{\frac{\Delta \quad {{VO}_{2}\left( {{Magnitude}\quad t_{1}\quad {to}\quad t_{3}} \right.}}{t_{3} - t_{1}}}{{\Delta XaO}_{2}\left( {{Magnitude}\quad t_{c}\quad {to}\quad t_{e}} \right)} = {\frac{\Delta \quad \overset{.}{V}{O_{2}\left( {{Magnitide}\quad t_{1}\quad {to}\quad t_{3}} \right)}}{\Delta \quad {{XaO}_{2}\left( {{Magnitide}\quad t_{c}\quad {to}\quad t_{e}} \right)}}.}}} & (29)\end{matrix}$

[0089] As with equation (28), equation (29) also represents a directcalculation for cardiac output because the unit represented by thenumerator are, for example, liters/second or liters/minute, and thedenominator is unitless. In these embodiments, the change in magnitudeof the oxygen uptake and fractional arterial oxygen concentration aremonitored during the oxygen modification step, which is why thistechnique is referred to in the preceding section heading as the“Magnitude of the Curve” technique.

[0090] D. Technique 4—Calculating Cardiac Output Based on the Volume ofBlood Flow

[0091] It is known that the volume of blood flowing through the heartduring a breathing cycle is defined as: $\begin{matrix}{V_{blood} = {\int_{t_{1}}^{t_{3}}{\frac{\Delta \quad \overset{.}{V}O_{2}}{\Delta \quad \overset{\_}{X}{aO}_{2}}\quad {{t}.}}}} & (30)\end{matrix}$

[0092] and the flow of blood, i.e., cardiac output, in liters perminute, for example, it defined as: $\begin{matrix}{Q_{blood} = {\frac{V_{blood}}{t}.}} & (31)\end{matrix}$

[0093] It can be appreciated that equation (30) can be substituted intoequation (31) to determine the cardiac output.

[0094] One embodiment of the present invention contemplates determiningthe baseline oxygen uptake and baseline arterial oxygen concentrationbefore performing the oxygen concentration modification step so that thechanges in oxygen uptake and baseline arterial oxygen concentrationresulting from the oxygen concentration modification step can becompared to this baseline. It is to be understood, however, that in analternative embodiment of the present invention, the baseline oxygenuptake and baseline arterial oxygen concentration are established afterthe effects of the oxygen concentration modification step; namely, afterthe patient's cardio-pulmonary system has returned to a steady statefollowing the oxygen concentration modification step.

[0095]FIGS. 11 and 12 schematically illustrate an exemplary embodimentof a cardiac output measurement device 30 used to implement theabove-described cardiac output measurement method. Cardiac outputmeasurement device 30 includes a patient flow measurement system 32 forquantitatively measuring the flow of gas to and from the patient and anoxygen analyzer 34 that measures the patient's fraction of inspiredoxygen (FIO₂). Patient flow measurement system 32 includes a flow sensor33, also referred to as a flow element, that creates a pressuredifferential for measuring the flow of gas passing through the flowelement. Oxygen analyzer 34 includes an oxygen analyzing element 35,which is essentially an airway adapter optical window and an O₂transducer having phototransmitter and photodector, that is used tomeasure the amount of oxygen passing in front of the optical window.Flow sensor 33 and oxygen analyzing element 35 are preferably locatedproximate to the patient's airway. The outputs of the patient flow andoxygen analyzing systems are provided to a microprocessor 36 forcalculating the patient's oxygen uptake.

[0096] Cardiac output measurement device 30 includes means 38 fordetecting a parameter indicative of the fractional arterial oxygenconcentration, XaO₂, of a patient. As noted above, this parameter is anyone of either SpO₂, SaO₂, PaO₂, or CaO₂. An example of a sensor thatmeasures SpO₂ is a conventional pulse oximeter, and a sensor thatmeasures SaO₂, PaO₂, or CaO₂ is a continuous indwelling catheter.Depending on the parameter measured, a conversion to XaO₂ may benecessary. This can be done, for example, by microprocessor 36. In theembodiment illustrated in FIG. 12, the pulse oximeter includes a pulseoximeter sensor 39 in contact with the patient to measure the oxygensaturation SpO₂ of patient 37.

[0097] The present invention contemplates that cardiac outputmeasurement device 30 includes an input/output interface 40 forcommunicating with the user. For example, a display or other indicatormay be provided that notifies the user when to induce that change inarterial oxygen concentration, as well as outputs the cardiacmeasurement result. A communication link 42 can also be provided fordownloading or receiving information and commands to or from a remotelocation.

[0098] One embodiment of the present invention contemplates that one ormore of the patient flow measurement system, the oxygen analyzingsystem, and the fractional arterial oxygen concentration measuringsystem can be implemented in a separate, stand-alone, module with theoutput of each being provided to processor 36. This enables differenttypes of patient flow, oxygen analyzing, and arterial oxygenconcentration measuring systems to be used with a common cardiac outputdetermination module. One benefit being that existing patient flowsensors, oxygen analyzers, and arterial oxygen concentration measuringsystems, such as a conventional pulse oximeter, can be used to providethe required inputs to the cardiac output module.

[0099] However, the present invention also contemplates that patientflow measuring system, the oxygen analyzing system, and arterial oxygenconcentration measuring system, or any combination thereof, can beintegrated into a single housing 43, as shown, for example, in FIG. 12.In this embodiment, the measuring elements of each system, such as theflow element 33, the airway adapter and O₂ transducer 35, and the pulseoximeter sensor 39, provide inputs, e.g., electronic, optical,pneumatic, or otherwise, to one or. more processing systems in housing43.

[0100] Also necessary for purposes of the present invention, as shown inFIG. 12, is a device or technique, generally indicated at 50, forinducing a change in the patient's arterial oxygen concentration. In theillustrated exemplary embodiment, device 50 is a rebreathing system thatcaptures the patient's expired gas in a collection reservoir 52. A valve54 controls the flow of gas, so that when the cardiac output system isnot actuated, the patient's airway communicates with ambient atmosphereor a conventional ventilator or pressure support system (not shown). Inthis embodiment, when the cardiac output is to be measured, valve 54 iscontrolled manually or via processor 36, to cause the patient's exhaledgas passed to reservoir 52 where it is collected. Because the gascollected in reservoir 52 has been exhaled by the patient, its oxygenconcentration is significantly reduced.

[0101] In a further embodiment of the present invention, a device 56 forremoving CO₂ is included in rebreathing system 50, so that thespontaneously breathing patient does not rebreathe significant amountsof CO₂. In a preferred embodiment of the present invention, device 56 isa CO₂ scrubber that removes CO₂ from the gas passing therethrough. Asnoted above, for a non-spontaneously breathing patient, CO₂ removaldevice 56 is optional, because their breathing pattern is controlled bythe ventilator regardless of the CO₂ levels inhaled by the patient.

[0102] Although the invention has been described in detail for thepurpose of illustration based on what is currently considered to be themost practical and preferred embodiments, it is to be understood thatsuch detail is solely for that purpose and that the invention is notlimited to the disclosed embodiments, but, on the contrary, is intendedto cover modifications and equivalent arrangements that are within thespirit and scope of the appended claims.

What is claimed is:
 1. A method for measuring cardiac output comprising:(1) quantitatively measuring a patient's airflow, a first parameterindicative of a percent oxygen inhaled and exhaled by such a patient,and a second parameter indicative of such a patient's fractionalarterial oxygen concentration; (2) inducing a change in such a patient'sarterial oxygen concentration; (3) repeating the airflow, the firstparameter and the second parameter measurements set forth in step (1);and (4) determining the patient's cardiac output based on the airflow,the first parameter, and the second parameter information collected insteps (1) and (3).
 2. The method according to claim 1, wherein thesecond parameter indicative of fractional arterial oxygen concentrationis one of SaO₂, PaO₂, CaO₂ or SpO₂.
 3. The method according to claim 1,wherein measuring the airflow includes providing a flow sensor proximateto such a patient's airway, wherein the flow sensor outputs a flowsignal indicative of a flow of breathing to or from such a patient. 4.The method according to claim 1, wherein measuring the first parameterincludes providing an oxygen analyzing element proximate to such apatient's airway, wherein the oxygen analyzing element outputs an oxygenconcentration signal indicative of an amount of oxygen in gas passingthrough the oxygen sensor.
 5. The method according to claim 1, whereinmeasuring the second parameter includes providing a pulse oximetersensor in contact with such a patient, wherein the pulse oximeter sensoroutput a signal indicative of an oxygen saturation SaO₂ of such apatient.
 6. The method according to claim 1, wherein inducing a changein such a patient's arterial oxygen concentration includes introducing anon-oxygen breathing gas into a stream of gas to be inhaled by such apatient.
 7. The method according to claim 1, wherein inducing a changein such a patient's arterial oxygen concentration includes rebreathinggas exhaled by such a patient.
 8. The method according to claim 7,wherein rebreathing includes removing carbon dioxide CO₂ from theexhaled gas before the exhaled gas is rebreathed.
 9. The methodaccording to claim 1, wherein determining the patient's cardiac outputincludes: determining a deviation of such a patient's oxygen uptake froma baseline oxygen uptake level occurring responsive to the inducedchange in such a patient's arterial oxygen concentration in step (2);determining a deviation of such a patient's arterial oxygenconcentration from a baseline arterial oxygen concentration leveloccurring responsive to the induced change in such a patient's arterialoxygen concentration in step (2); and comparing the deviation in oxygenuptake to the deviation in arterial oxygen concentration.
 10. The methodaccording to claim 9, wherein determining the deviation of such apatient's oxygen uptake includes determining an effective area betweenthe baseline oxygen uptake level and an oxygen uptake curve occurringresponsive to the execution of step (2), and wherein determining thedeviation of such a patient's arterial oxygen concentration includesdetermining an effective area between the baseline arterial oxygenconcentration level and an arterial oxygen concentration curve occurringresponsive to the execution of step (2).
 11. The method according toclaim 9, wherein determining the deviation of such a patient's oxygenuptake includes determining a slope of a line extending between thebaseline oxygen uptake level and a point on an oxygen uptake curveoccurring responsive to the execution of step (2), and whereindetermining the deviation of such a patient's arterial oxygenconcentration includes determining a slope of a line extending betweenthe baseline arterial oxygen concentration level and a point on anarterial oxygen concentration curve occurring responsive to theexecution of step (2).
 12. The method according to claim 9, whereindetermining the deviation of such a patient's oxygen uptake includesdetermining a magnitude between the baseline oxygen uptake level and apoint on an oxygen uptake curve occurring responsive to the execution ofstep (2), and wherein determining the deviation of such a patient'sarterial oxygen concentration includes determining a magnitude betweenthe baseline arterial oxygen concentration level and a point on anarterial oxygen concentration curve occurring responsive to theexecution of step (2).
 13. The method according to claim 1, furthercomprising outputting, in human perceivable form, an indication of thecardiac output determined in step (4).
 14. An apparatus for measuringcardiac output comprising: a patient flow measuring system adapted toquantitatively measuring a patient's airflow; an oxygen analyzing systemadapted to measure a first parameter indicative of a percent oxygeninhaled and exhaled by such a patient; means for measuring a secondparameter indicative of such a patient's fractional arterial oxygenconcentration; means for inducing a change in such a patient's arterialoxygen concentration; a processor adapted to determine such a patient'scardiac output based on the output of the measured airflow, the firstparameter, and the second parameter; and outputting means for outputtinga result indicative of such a patient's cardiac output in humanperceivable form.
 15. The apparatus according to claim 14, wherein themeans for measuring the second parameter is a pulse oximetry systemincluding a pulse oximeter sensor in contact with such a patient. 16.The apparatus according to claim 14, wherein the second parameterindicative of fractional arterial oxygen concentration is one of SaO₂,PaO₂, CaO₂ or SPO₂.
 17. The apparatus according to claim 14, wherein thepatient flow measuring system includes a flow sensor disposed proximateto such a patient's airway such that gas inhaled and exhaled by thepatient passes through the flow sensor.
 18. The apparatus according toclaim 14, wherein the oxygen analyzing system includes and oxygenanalyzing element comprising (a) an airway adapter having an opticalwindow and (b) an oxygen transducer having an photoemitter and aphotodetector, and wherein the oxygen analyzing element is disposedproximate to such a patient's airway such that gas inhaled and exhaledby such a patient passes in front of the optical window.
 19. Theapparatus according to claim 14, wherein the means for inducing a changein such a patient's arterial oxygen concentration comprises a system forintroducing a non-oxygen breathing gas into a stream of gas to beinhaled by such a patient.
 20. The apparatus according to claim 14,wherein the means for inducing a change in such a patient's arterialoxygen concentration comprises a rebreathing system for causing such apatient to rebreathe gas exhaled by such a patient.
 21. The apparatusaccording to claim 20, wherein the rebreathing system further comprisesmeans for removing carbon dioxide CO₂ from the exhaled gas before theexhaled gas is rebreathed.
 22. The apparatus according to claim 14,wherein the processor determines: (a) a deviation of such a patient'soxygen uptake from a baseline oxygen uptake level occurring responsiveto an induced a change in such a patient's arterial oxygenconcentration; (b) a deviation of such a patient's arterial oxygenconcentration from a baseline arterial oxygen concentration leveloccurring responsive to an induced a change in such a patient's arterialoxygen concentration; and (c) compares the deviation in oxygen uptake tothe deviation in arterial oxygen concentration.
 23. The apparatusaccording to claim 22, wherein the processor determines the deviation ofsuch a patient's oxygen uptake by determining an effective area betweenthe baseline oxygen uptake level and an oxygen uptake curve occurringresponsive to the induced change in such a patient's arterial oxygenconcentration, and determines a deviation of such a patient's arterialoxygen concentration by determining an effective area between thebaseline arterial oxygen concentration level and an arterial oxygenconcentration curve occurring responsive to the induced change in such apatient's arterial oxygen concentration.
 24. The apparatus according toclaim 22, wherein the processor determines the deviation of such apatient's oxygen uptake by determining a slope of a line extendingbetween the baseline oxygen uptake level and a point on an oxygen uptakecurve occurring responsive to the induced change in such a patient'sarterial oxygen concentration, and determines the deviation of such apatient's arterial oxygen concentration by determining a slope of a lineextending between the baseline arterial oxygen concentration level and apoint on an arterial oxygen concentration curve occurring responsive tothe induced change in such a patient's arterial oxygen concentration.25. The apparatus according to claim 22, wherein the processordetermines the deviation of such a patient's oxygen uptake bydetermining a magnitude between the baseline oxygen uptake level and apoint on an oxygen uptake curve occurring responsive to the inducedchange in such a patient's arterial oxygen concentration, and determinesthe deviation of such a patient's arterial oxygen concentration bydetermining a magnitude between the baseline arterial oxygenconcentration level and a point on an arterial oxygen concentrationcurve occurring responsive to the induced change in such a patient'sarterial oxygen concentration.